Furthermore, SARS-CoV-2 was associated with higher 30-day mortality as compared with influenza (adjusted HR (aHR) 4.43, 95%?CI 3.51 to 5.59), RSV (aHR 3.81, 95%?CI 2.72 to 5.34) and other respiratory viruses (aHR 3.46, 95%?CI 2.61 to 4.60), as well as higher 90-day mortality, ICU admission, ICU mortality and pulmonary embolism in adults. In children, patients with SARS-CoV-2 were older and had lower prevalence of chronic cardiac and respiratory diseases compared with other viruses.
SARS-CoV-2 is associated with more severe outcomes compared with other respiratory viruses, and although associated with specific patient and clinical characteristics at admission, a substantial overlap precludes discrimination based on these characteristics.
SARS-CoV-2 is associated with more severe outcomes compared with other respiratory viruses, and although associated with specific patient and clinical characteristics at admission, a substantial overlap precludes discrimination based on these characteristics.Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterised by exuberant tissue remodelling and associated with high unmet medical needs. Outcomes are even worse when IPF results in secondary pulmonary hypertension (PH). Importantly, exaggerated resistance to cell death, excessive proliferation and enhanced synthetic capacity are key endophenotypes of both fibroblasts and pulmonary artery smooth muscle cells, suggesting shared molecular pathways. Under persistent injury, sustained activation of the DNA damage response (DDR) is integral to the preservation of cells survival and their capacity to proliferate. Checkpoint kinases 1 and 2 (CHK1/2) are key components of the DDR. The objective of this study was to assess the role of CHK1/2 in the development and progression of IPF and IPF+PH.
Increased expression of DNA damage markers and CHK1/2 were observed in lungs, remodelled pulmonary arteries and isolated fibroblasts from IPF patients and animal models. Blockade of CHK1/2 expression or activity-induced DNA damage overload and reverted the apoptosis-resistant and fibroproliferative phenotype of disease cells. Moreover, inhibition of CHK1/2 was sufficient to interfere with transforming growth factor beta 1-mediated fibroblast activation. Importantly, pharmacological inhibition of CHK1/2 using LY2606368 attenuated fibrosis and pulmonary vascular remodelling leading to improvement in respiratory mechanics and haemodynamic parameters in two animal models mimicking IPF and IPF+PH.
This study identifies CHK1/2 as key regulators of lung fibrosis and provides a proof of principle for CHK1/2 inhibition as a potential novel therapeutic option for IPF and IPF+PH.
This study identifies CHK1/2 as key regulators of lung fibrosis and provides a proof of principle for CHK1/2 inhibition as a potential novel therapeutic option for IPF and IPF+PH.Acute exacerbations of interstitial lung diseases (AE-ILD) have a high mortality rate with no effective medical therapies. Lung transplantation is a potentially life-saving option for patients with AE-ILD, but its role is not well established. The aim of this study is to determine if this therapy during AE-ILD significantly affects post-transplant outcomes in comparison to those transplanted with stable disease.
We conducted a retrospective study of consecutive patients with AE-ILD admitted to our institution from 2015 to 2018. The comparison group included patients with stable ILD listed for lung transplant during the same period. https://www.selleckchem.com/products/leukadherin-1.html The primary end-points were in-hospital mortality for patients admitted with AE-ILD and 1-year survival for the transplanted patients.
Of 53 patients admitted for AE-ILD, 28 were treated with medical therapy alone and 25 underwent transplantation. All patients with AE-ILD who underwent transplantation survived to hospital discharge, whereas only 43% of the AE-ILD medically treated did. During the same period, 67 patients with stable ILD underwent transplantation. Survival at 1?year for the transplanted patients was not different for the AE-ILD group versus stable ILD group (96% vs 92.5%). The rates of primary graft dysfunction, post-transplant hospital length-of-stay and acute cellular rejection were similar between the groups.
Patients with ILD transplanted during AE-ILD had no meaningful difference in overall survival, rate of primary graft dysfunction or acute rejection compared with those transplanted with stable disease. Our results suggest that lung transplantation can be considered as a therapeutic option for selected patients with AE-ILD.
Patients with ILD transplanted during AE-ILD had no meaningful difference in overall survival, rate of primary graft dysfunction or acute rejection compared with those transplanted with stable disease. Our results suggest that lung transplantation can be considered as a therapeutic option for selected patients with AE-ILD.This study aimed to determine whether a 6-week behaviour change intervention was more effective than a sham intervention for reducing sedentary behaviour (SB) in people with chronic obstructive pulmonary disease (COPD).
People with stable COPD on the waitlist for entry into pulmonary rehabilitation were recruited to this multicentre trial with randomisation (independent, concealed allocation) to either an intervention group or sham group, assessor blinding and intention-to-treat (ITT) analysis. The behaviour change intervention consisted of once weekly sessions for 6?weeks with a physiotherapist to reduce SB through education, guided goals setting and real-time feedback on SB. The sham intervention consisted of once weekly phone calls for 6?weeks to monitor health status. SB was measured continuously over 7?days using thigh-worn accelerometry (activPAL3 micro). The primary outcome was time spent in SB. Participants with at least 4?days of ?10?hours waking wear time were included in the ITT analysis and those who reported achieving ?70% of goals to reduce SB or who completed all sham calls were included in a per-protocol analysis.
70 participants were recruited and 65 completed the study (mean±SD?age 74±9 years, mean FEV55%±19% predicted, 49% male). At 6?weeks, no between-group differences in time spent in SB were observed in the ITT analysis (mean difference 5?min/day, 95%?CI -38 to 48) or per-protocol analysis (-16?min/day, 95%?CI -80 to 48).
A 6-week behaviour change intervention did not reduce time in SB compared with a sham intervention in people with stable moderate-to-severe COPD prior to pulmonary rehabilitation.
A 6-week behaviour change intervention did not reduce time in SB compared with a sham intervention in people with stable moderate-to-severe COPD prior to pulmonary rehabilitation.